How to modulate inflammatory cytokines in liver diseases

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Abstract
Most acute and chronic liver diseases are characterized by inflammatory processes with enhanced expression of various pro‐ and anti‐inflammatory cytokines in the liver. These cytokines are the driving force of many inflammatory liver disorders often resulting in fibrosis and cirrhosis.Severe alcoholic hepatitis is a prototypic tumor necrosis factor‐α (TNF‐α)‐associated disease. This knowledge has recently led to pilot studies with promising results investigating specific anti‐TNF drugs such as infliximab or etanercept in the treatment of this disease, although a recently performed controlled French study did show a potential detrimental effect of this approach. Anti‐TNF treatment strategies might also improve chronic hepatitis C infection as shown by one controlled trial using etanercept administered subcutaneously for 24 weeks. Furthermore, several case reports suggest that TNF‐α neutralization is not harmful to patients chronically infected with this virus. In contrast, neutralization of TNF‐α worsens and might even be associated with fatalities in chronic hepatitis B infection. Anti‐inflammatory cytokines such as interleukin‐10 (IL‐10) have also been tried in patients with chronic liver diseases. Whereas IL‐10 administered to patients with chronic hepatitis C virus infection shows indeed anti‐inflammatory effects in the liver, it seems to act as a proviral agent thereby limiting its clinical utility. Another cytokine with major anti‐inflammatory potential is the adipokine adiponectin, as its administration is beneficial in many experimental models of liver injury. Interference with cytokine pathways and/or administration of anti‐inflammatory cytokines will be of major interest in the future therapy of many liver diseases.

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